The EDiHTA project aims to deliver an innovative health technology assessment (HTA) framework for digital health technologies (DHT) that integrates existing methods with new ones to inform decision-making across Europe at different levels. In the development phase of the EDiHTA framework, it has been essential to identify all relevant stakeholders and their roles in the innovation process, while also capturing their needs and requirements.

The Innovation of Health Technology Assessment Methods framework was applied to identify relevant stakeholders and their needs and requirements regarding the design of the EDiHTA framework. Once stakeholders and their roles (practitioners or beneficiaries) were identified, their needs were assessed by reviewing existing and new HTA methodologies for DHT as used in 17 countries across Europe. Future scenarios were examined and gaps to be addressed were determined. Various methods were used to elicit the views of different stakeholders (policymakers, HTA agencies and bodies, industry, healthcare professionals, patients). including literature reviews, two online surveys, semi-structured online interviews, and focus groups.

We engaged policymakers from 15 European countries; 15 HTA agencies from nine European countries; 29 developers (startups and big companies) from 10 different European markets; 14 healthcare professionals from nine European countries plus eight from Brazil, Canada, and the USA; and 15 patient representatives from 10 European countries. The analysis highlighted the heterogeneity among European health systems in assessing, implementing, and reimbursing DHT. All stakeholder groups emphasized the need for a harmonized HTA framework to assess DHT efficiently and accurately, including elements specific to DHT, such as cybersecurity, economic and organizational impact, and patient-centered outcomes.

There is a clear need among European stakeholders for an agile, flexible, and multidimensional HTA framework that facilitates stepwise assessments across the technology life cycle and involves all relevant stakeholders in the assessment to inform decision-making. The stakeholder interaction also identified new HTA topics and domains essential for effectively addressing the unique challenges of DHT within the EDiHTA framework.

Ethical, legal, social, and organizational (ELSO) issues are increasingly recognized in health technology assessment (HTA). However, information retrieval methods for ELSO aspects are scarce, and there are no widely accepted standard methods for developing these analyses. Here, we present the methodology and results of the ELSO analysis included in two HTA reports developed in 2024.

Two HTA reports were developed to analyze the value of: (i) genetic testing in congenital hearing loss (cHL); and (ii) a minimally invasive tissue sampling (MITS) technique to determine cause of death. ELSO domains were considered necessary for decision-making. To address the assessment, we conducted scoping reviews to synthesize the evidence, following the PRISMA Extension for Scoping Reviews, and used a prespecified extraction sheet for defining facilitators and barriers. The literature searches included specific search filters for ELSO issues developed by HTA information specialists from the Spanish Network of Agencies for Health Technology Assessment (RedETS).

The scoping review for ELSO issues in genetic testing for cHL identified 452 references. After eligibility assessment, four reports were included, providing eight ELSO issues: two organizational, two social, and four ethical. Six concerns were facilitators and two were barriers to implementing genetic testing in cHL. The scoping review for ELSO issues in the MITS to determine cause of death identified 903 references. After eligibility assessment, 25 reports were included, bringing forth 43 ELSO concerns: 18 organizational, 15 social, seven ethical, and three legal. Twenty-three issues were facilitators and 20 may be barriers to implementing MITS.

The analysis of ELSO domains through a scoping review provided crucial information for implementing the two selected technologies. However, challenges remain in ELSO information retrieval: (i) key concepts related to ELSO concerns could be described in a variety of ways; and (ii) ELSO terms are not being used or indexed consistently.

Assessing the risk of bias (RoB) using validated tools is an important aspect of any health technology assessment (HTA). However, many of these tools were designed with pharmaceuticals in mind. Well conducted trials of medical devices often face different challenges. Consequently, choosing the RoB tool to use in any assessment may play a large role in how evidence of such technologies is perceived.

A systematic review and meta-analysis was conducted on renal denervation devices for treating uncontrolled hypertension. Only randomized controlled trials (RCTs) were included, so the revised Cochrane RoB tool was chosen to assess bias in individual studies. RoB assessments were undertaken by two reviewers.

Twenty-five RCTs met the eligibility criteria for the systematic review and were assessed for RoB. Application of the revised Cochrane RoB tool resulted in some disparity in the final assessments, compared with the quality criteria for RCTs defined in previously published clinical guidelines for hypertension. Specifically, some of the sham-controlled RCTs had an overall RoB rating of “some concerns”, whereas some of the open-label RCTs had a low RoB and the tool seemed unable to distinguish between the designs. Given that sham-controlled trials can control for a potential placebo effect, this result was both unexpected and unintuitive.

Designing RCTs for medical devices requires substantial input, planning, and consideration from multiple stakeholders. Assessing the RoB of such studies, although necessary from a decision-maker perspective, requires careful contextual interpretation to understand and fully appreciate the nuances at play. Potential for a new RoB tool for assessing studies of medical devices is warranted.

Cutaneous leishmaniasis (CL) is a neglected endemic disease in several states in Brazil. The direct costs of CL treatment from the patient’s perspective can be significant, as can the indirect costs, which include the various non-medical expenses and loss of income incurred during treatment. The study objective was to identify the direct and indirect costs during the treatment of cutaneous leishmaniasis from the patient perspective.

A cross-sectional study was conducted at the René Rachou Institute/Fiocruz between April 2022 and April 2023 and included patients with a confirmed diagnosis of CL. Participants were interviewed during the treatment period to assess direct medical and non-medical costs as well as indirect costs associated with treatment. Direct costs were estimated using the micro-costing approach and indirect costs were estimated using the human capital method. Descriptive analyses and hypothesis tests were performed for associations between costs and sociodemographic and clinical variables, with a statistical significance level of five percent. The study had ethical approval (CAAE 28929220.0.0000.5091).

The study included 68 patients, predominantly male (77.9%) with an average age of 53 years. CL was the most common clinical form (76.4%), with new cases accounting for 79.4 percent of participants. Direct costs per treatment cycle averaged USD117.36, resulting from transportation, food, and medical examinations. Indirect costs from lost workdays amounted to USD9,936.58, with an average of USD160.12 per patient. Catastrophic expenditure (>10% of monthly income) was observed in 41.9 percent of families. This was significantly associated with direct cost, bacterial infection, and sociodemographic factors such as sex, age, and distance traveled.

This study confirmed that treatment for CL, although free in the Brazilian health system, generates significant direct and indirect costs for patients. The highest costs are related to travel and accommodation resulting from the centralized healthcare model, where treatment is not available close to where patients live.

In 2023, we published widely cited cost-effectiveness thresholds (CETs) for 174 countries. This update refined our approach by incorporating gross domestic product (GDP) growth projections to adjust target increases in life expectancy and health expenditure. This methodology provides more precise estimates tailored to the economic and health contexts of individual countries, enabling better informed resource allocation decisions.

We revised our 2023 methodology by integrating International Monetary Fund projections of GDP growth for the next five years to establish customized targets for life expectancy (LE) and health expenditure (HE) growth. This update accommodates countries where the prior assumption of median growth within income groups was less applicable. The CETs were derived so that the effect of new interventions on the evolution of LE and HE is set within predefined goals. To provide guidance on CETs, we projected country-level HE and LE increases by income level based on World Bank data to ensure the estimates align with individual country realities.

The updated thresholds yielded values consistent with our 2023 estimates, yet notable differences emerged in countries with distinct GDP growth trajectories or unique health spending patterns. For example, thresholds for India and similar countries adjusted upward to reflect ambitious yet realistic targets for HE and LE growth. Across 174 countries, most thresholds remained below one GDP per capita, confirming their relevance for guiding economic evaluations. These nuanced updates demonstrate the flexibility and applicability of our approach in diverse contexts, particularly for low- and middle-income countries.

By incorporating GDP growth projections, this study enhanced the precision of cost-effectiveness thresholds, ensuring their applicability across varying country contexts. These updates provide critical guidance for health systems aiming to balance efficiency, equity, and sustainability, particularly in resource constrained settings.

Sensory burden, a momentary experience of being bothered by sensory stimuli, is a frequent challenge following acquired brain injury (ABI). This study quantitatively tested a theoretical model conceptualizing sensory burden as a dynamic interaction between situational triggers and an individual’s biopsychosocial resources using an experience sampling method.

41 individuals with ABI (median age = 59 years, median time since injury = 6.3 years) provided real-time data at seven semi-random intervals per day over seven consecutive days. Multilevel regression modeling assessed the influence of situational triggers (setting, company, effort, activity dissatisfaction, and negative affect) and individual resources (processing speed, fatigue, and sleep quality) on sensory burden.

Momentary fluctuations in sensory burden varied in severity and variability across individuals. Sensory burden was associated with higher levels of negative affect (β = .58, p < .01), activity dissatisfaction (β = .07, p < .01), effort (β = .09, p < .01), and being in company (β = .39, p < .01). Moreover, sensory burden was related to slower processing speed (β = −0.04, p = .02) and higher fatigue (β = .19, p < .01). However, no interaction effects were found. Effort was the only positive, significant between-person predictor (β = .56, p < .01).

These findings underscore the dynamic and individualized nature of sensory burden after ABI, emphasizing the need for personalized interventions targeting sensory hypersensitivity. Future research should explore additional triggers, resources, and causal pathways to further elucidate the proposed mechanisms and inform treatment development.

Patient and public involvement (PPI) is becoming increasingly embedded in research. While financial constraints are cited as barriers to PPI, there is a lack of understanding of its financial affordability and factors influencing costs. This work aimed to: (i) clarify PPI board costs; (ii) find cost-saving opportunities; and (iii) provide a cost template for others to implement a PPI board.

A cost analysis was conducted to identify the financial capital and staffing hours required to establish and maintain a PPI board. This analysis involved the following steps: (i) identifying the stages of the project; (ii) outlining the activities associated with each stage; (iii) establishing the time frame for each stage and its activities; (iv) identifying the necessary positions; and (v) calculating the associated costs.

The board’s design, implementation, one-year operation, and evaluation cost AUD150,229 (EUR84,076.41) (43% for design, 21% for implementation, 19% for operation, and 17% for evaluation). Although the distribution of hours allocated per position was consistent with the distribution of costs, the results varied by stage. The highest proportion of hours (and costs) on design (67%) and implementation (46%) were attributed to the head researcher position, whereas the research assistant had the highest proportion of hours for operations (53%). The board members accounted for the lowest proportion of the total hours (5%). No time was allocated to them during the design or evaluation phase, and only 11 and 14 percent were attributed to them for implementation and operation, respectively.

The absence of PPI representatives and junior researchers in the design and evaluation stages led to higher costs and some inconsistencies with the PPI model, which requires public involvement from the outset of any project. A deeper level of PPI from the design of this project would not only make it more financially efficient but also, even more critically, enhance and ensure community engagement.

Lack of persistence and adherence to growth hormone therapy negatively impacts growth outcomes. Real-world international studies report that a significant proportion of children discontinue somatropin treatment. However, this information is not available for Argentina. The aim of this study was to describe the persistence and reasons for discontinuation of somatropin treatment in pediatric patients in the real-world setting of Argentina.

This retrospective cohort study analyzed data from the Anhelos program (Argentina) to evaluate somatropin treatment in children under 16 years of age. Persistence and treatment discontinuation were measured, with causes classified as medical or non-medical. Statistical methods were used to analyze predictive factors such as sex, age, diagnosis, region, and healthcare coverage. Persistence was analyzed using Kaplan-Meier, while discontinuation was studied through logistic regression and Cox proportional hazards models. SPSS v26.0 was used, with significance defined as p-value≤0.05.

We analyzed 1,159 patients, 42.8 percent of whom were female; 58.7 percent were aged eight years or younger. A total of 56.7 percent discontinued somatropin treatment at least once. No significant differences were observed in sex, age, or region between those who interrupted treatment and those who did not. However, differences were found based on diagnosis and healthcare coverage. Non-medical causes accounted for 64.6 percent of treatment discontinuations, primarily due to delivery issues. Public healthcare coverage was associated with a higher likelihood of discontinuation and lower treatment persistence than social security or private health insurance coverage.

Our data suggested a high rate of at least one treatment discontinuation among pediatric patients in Argentina receiving somatropin, primarily driven by non-medical causes.

Decision-making in the context of health technology assessment (HTA) of gene therapies for hemophilia needs to be tailored toward patients’ preferences. To promote equitable and patient-centered decision-making, it is crucial to provide patients with culturally attuned educational materials to ensure comprehension of key aspects of gene therapy so they can make legitimate and informed treatment decisions based on their preferences.

In this mixed methods study, we used a contextualization approach to translate the educational tool from the PAVING study (Patient Preferences to Assess Value IN Gene Therapies in Hemophilia) into Brazilian Portuguese. Translated versions were reviewed by a hematologist, a patient association representative, and two industry professionals. The tool was subsequently piloted with two people with hemophilia (PWH). After revisions, the tool was virtually presented to 12 PWH to transfer knowledge in preparation for the interview about their willingness to receive gene therapy. They were also required to perform the attribute-ranking exercise from the PAVING study.

The translation process led to minor adaptations required for local context. The original version designed for computer use was adapted for use on a mobile phone. Pilot testing with PWH resulted in minor changes to optimize clickstreams. Ten participants indicated some baseline awareness of gene therapy for hemophilia (good n=2; reasonable n=3; bad or very bad n=5). Participants indicated a general willingness to receive gene therapy (very willing n=7; willing n=2; neutral n=3). The six top-ranked treatment attributes were “effect on factor level,” “dose frequency,” “impact on daily life,” “probability that prophylaxis can be stopped after treatment,” and “effect on annual bleeding rate.”

These findings may contribute to further developments of the design and contextualization of hemophilia educational resources of gene therapy. The preliminary results on patient preferences will also inform future quantitative preference studies to be considered in the decision-making related to individual care and to reimbursement and coverage decisions in health systems, thus incorporating the patient perspective in HTA processes.

Clinical assessment is a continuous process during the life cycle of a medical device for obtaining evidence about performance, safety, demand, and effectiveness in patient care. The objective of this work was to carry out the clinical evaluation of a sample of 66 mechanical ventilators from the National Institute of Respiratory Diseases in Mexico.

The multi-criteria decision analysis method was used. Eleven variables were defined: three related to the patient (number of patients treated, illness, and average length of stay), and eight related to the medical device (amount, location, type, function, use hours, out of service hours, brand, and model). Three partial indicators were developed to evaluate availability, demand, and operation aspects of the medical device. These partial indicators were integrated into a global indicator called clinical use. The numerical result was interpreted with a qualitative scale defined with four levels of clinical use (low, regular, medium, and high). Data from the year 2023 were used.

The sample evaluated contained seven brands and 12 different models of mechanical ventilators. Forty-two percent were classified as low clinical use (they are underutilized) and 39 percent were regular clinical use. These two results indicated that these 54 devices have a low impact on patient care. On the other hand, only 11 percent had medium use and 8 percent had high use. In this last case, we must note the overuse of these five ventilators; that is, they were used almost 24 hours a day in patient care.

Sixty-two devices in the sample had a clinical use that allowed them to be available for mechanical ventilation of patients with respiratory conditions that require it. In the case of ventilators with high clinical use, technological improvements due to the brand had an influence on their constant use, allowing effective care for the patients in critical condition.

People frequently use litigation to access technologies in Brazil. From 2020 to 2023 there was a 38 percent increase in the lawsuits requesting drugs (55,600 to 76,700). The Ministry of Health’s expenditure on litigation reached USD428 million in 2023. This study analyzed the decision issued on September 2024 by the Brazilian Supreme Court (STF) to address litigation.

The study reviewed the STF decision, identifying the requirements for judicial provision of medicines not incorporated into the public health system that are directly related to the health technology assessment process.

By a 10-to-one majority, the STF decided that medicines not incorporated into the public health system should not be judicially granted. Exceptions apply to medicines registered by the National Health Surveillance Agency and are based on several criteria: evidence of illegality in a decision by the National Committee for Health Technology Incorporation (CONITEC) or excessive delays in its analysis; lack of substitutes in the public health system; or scientific evidence of efficacy and safety. It was also concluded that CONITEC’s recommendation not to incorporate a drug should be considered, and that when a drug is judicially granted it could be submitted to CONITEC for assessment.

The STF decision seeks to guarantee both the right to health and the financial sustainability of the public health system. By requiring robust scientific evidence for judicially granted medicines, it underscores CONITEC’s crucial role and the need for evidence-based decision-making at an individual level. Its determination also pushes for greater coordination between the Judiciary and Executive Branches of the government.

Artificial intelligence (AI) in health technology assessment (HTA) report development addresses three needs: accelerating processes via automation, standardizing tools for quality and consistency, and training to responsibly integrate generative AI. Conducted at the Agency for Health Quality and Assessment of Catalonia (AQuAS), this study identified tasks that generative AI can enhance and evaluated the team’s perceptions, knowledge, attitudes, and experience with these tools.

A review of technical literature and an exploration of leading tools, including ChatGPT and Copilot, were conducted to identify relevant functionalities and their potential applications in HTA. Additionally, an online survey was designed to assess the team’s knowledge and use of AI with four sections: (i) team characteristics; (ii) knowledge and use of generative AI; (iii) practical applications and perceived utility in specific tasks; and (iv) perspectives on potential and adoption barriers. Created using Microsoft Forms, the survey was distributed in October 2024.

An initial best practices guide was developed, detailing how to interact with generative AI tools, key elements for integration, and practical application examples, including training materials to mitigate risks. The survey achieved a 100 percent response rate, with participation from the entire evaluation team (n=14) and administrative support (n=1). Of respondents, 53 percent reported intermediate knowledge, 80 percent use these tools in daily tasks, and 41 percent have used them for over a year. Among users (n=12), key tasks included text drafting (92%), information retrieval (83%), and PDF reading (67%). Participants reported high satisfaction, and non-users expressed willingness to adopt these tools.

Generative AI showed great potential to enhance efficiency and quality in report development at AQuAS. High satisfaction among current users and a willingness to adopt it by non-users supported its implementation. The initial best practices guide and ongoing training will be essential to standardize the use of AI and maximize its impact.

To identify challenges in adopting new methodologies for assessing medical devices we aimed to explore underlying views of health technology assessment (HTA) practitioners about appropriate methodology at HTA agencies. Inspired by the “values in doing assessments of health technologies” (VALIDATE) approach, we focused on the role of normative commitments of HTA practitioners in the adoption of new methods.

Based on desk research, an online survey (including questions on procedures, scoping, and assessments of high risk medical devices) was developed and sent to members of the International Network of Agencies for Health Technology Assessment. Semi-structured interviews were conducted with survey respondents involved in assessments of transcatheter aortic valve implantation to gain an in-depth understanding of choices made and views about assessing medical devices. Data collection occurred between January and May 2023. Descriptive statistics were used to summarize survey findings, thematic analysis for the interviews, and the Consolidated Criteria for Reporting Qualitative Research checklist was used for reporting.

Twenty-two out of 50 survey invitees responded, and 15 indicated they assessed medical devices. Among these, eight were willing to be interviewed, of which four accepted the interview invitation. The consolidated results showed that the current practice of assessing medical devices at HTA agencies is predominantly based on procedures, methods, and epistemological principles developed for assessments of drugs. Both practical factors (available time, demands of decision-makers, existing legal frameworks, and HTA guidelines), as well as the commitment of HTA practitioners to principles of evidence-based medicine, made the adoption of new HTA methodology difficult.

There is broad recognition that assessments of medical devices may require changes in HTA methodology. To realize this, the HTA community may need to discuss the role, responsibility, and goals of HTA, and to inform decisions on how to implement new HTA processes and methods for assessing devices.

In recent years, there has been an increase in judicial claims in Uruguay seeking pembrolizumab-axitinib for the treatment of advanced kidney cancer. Understanding the characteristics and clinical evolution of patients accessing this medication through judicial rulings is essential to support health policies based on real-world evidence (RWE).

This study aimed to describe the sociodemographic and clinical characteristics, as well as global survival, of patients diagnosed with advanced clear cell renal carcinoma who received pembrolizumab-axitinib through judicial claims against the National Resources Fund (Fondo Nacional de Recursos) in Uruguay between 2020 and 2022. Patients with a favorable judicial ruling during the study period who received at least one dose of the combination therapy were included. Descriptive analyses of sociodemographic and clinical characteristics were conducted, and survival was estimated using the Kaplan-Meier method.

Between 2020 and 2022, 46 patients received pembrolizumab-axitinib treatment through judicial claims for advanced clear cell renal carcinoma. The average age of the patients, who were predominantly male, was 55.6 years. Most patients were from the private healthcare sector, with a similar distribution between the capital and the interior of the country. The survival analysis showed a global survival rate of 84.8 percent at 12 months (95% confidence interval [CI]: 70.7, 92.4), 78.3 percent at 24 months (95% CI: 61.8, 88.3), and 67.1 percent at 36 months (95% CI: 38.8, 84.5).

This real-world study provided promising results regarding the effectiveness of pembrolizumab-axitinib treatment in the Uruguayan healthcare context. The findings favored the opportunity to incorporate this therapy for advanced kidney cancer into the Comprehensive Health Care Plan. Additionally, it highlighted the importance of RWE in supporting healthcare policy decisions.

Health technology assessments (HTAs) are essential for evidence-informed decision-making. In urgent clinical scenarios, ultra-rapid HTAs provide concise evaluations to guide patient-specific decisions in 72 hours. The Institute for Clinical Effectiveness and Health Policy (IECS), with over 20 years of experience in HTA, has played a key role in delivering these rapid assessments to support efficient healthcare decisions in Argentina.

A descriptive analysis was conducted using the registry of ultra-rapid HTA reports produced by the IECS from April 2012 to August 2024. Two independent researchers extracted data from the historical database where the data on requests are stored. The database contains information about the requesters, type of technology, pathology, request dates, and delivery dates. The researchers categorized the information by type of technology (drugs, devices, procedures, diagnostics), therapeutic area (surgery, cardiovascular, infections, neurology, endocrinology, metabolic disorders, etc.), disease type (rare or not), and the requester of the report. The data were analyzed quantitatively.

Over 12 years, IECS produced 544 ultra-rapid HTA reports. The most requested therapeutic areas were oncology (n=124; 23%), neurology (n=94; 17%), musculoskeletal (n=45; 8%), other (n=39; 7%), and ophthalmology (n=31; 6%). Evaluated technologies primarily included drugs (n=255; 47%), followed by procedures (n=152; 28%), devices (n=70; 13%), and diagnostic tests (n=67; 12%). Reports on orphan diseases represented 19 percent of the total. Most requests were submitted by social health insurance providers (n=413; 76%), private insurers (n=123; 23%), hospitals (n=7; 1%), and the Ministry of Health (n=1).

The IECS analyzed 544 ultra-rapid HTA reports, showing a growing demand for timely evaluations, especially in oncology and neurology. Only 19 percent focused on orphan diseases, with most addressing prevalent conditions. These findings underscore the need for rapid assessment to support decision-making by social health insurers, improve access to critical technologies, and achieve a more equitable, transparent, and fair health system.

In South Korea, health technology assessment (HTA) evaluates the safety, efficacy, and cost effectiveness of technologies reimbursed by national health insurance. The National Evidence-Based Healthcare Collaborating Agency (NECA) engages the public and patients in HTA to enhance transparency and relevance. This study examined intra-articular corticosteroid injections (IACS) for knee osteoarthritis and radiofrequency ablation (RFA) for thyroid nodules to illustrate the role of diverse stakeholder input in decision-making.

Public Participation for IACS: IACS is a familiar treatment for knee osteoarthritis in Korea and has been used extensively for decades. To capture public perceptions, a structured survey was conducted to identify concerns about treatment frequency, safety, and efficacy. Findings were synthesized with systematic reviews to create public-friendly materials such as infographics, videos, and social media content.

Patient Participation for RFA: RFA, a non-reimbursed procedure for thyroid nodules, required direct input from patients to assess its value. Semi-structured interviews with RFA recipients explored their decision-making priorities, such as symptom relief, cosmetic concerns, and post-procedure recovery. These insights informed the evaluation framework for RFA in HTA.

Public surveys on IACS emphasized the need for clearer guidelines about dosing and safety, particularly for repeat injections. Systematic reviews showed limited evidence on long-term adverse effects, prompting further research. Educational materials enhanced public awareness of risks and benefits, supporting informed choices.

Interviews with patients who had received RFA revealed unique challenges and shared concerns specific to thyroid conditions, such as post-procedure discomfort and symptom management priorities. These insights, including preferences for nodule size reduction and recurrence rates, aligned with expert-defined outcome priorities, validating patient-reported outcomes in HTA. These findings led to a conditional recommendation balancing clinical value and misuse prevention.

Integrating public and patient voices into HTA strengthens evidence generation and fosters trust in health policy decisions. By addressing diverse stakeholder concerns, NECA aims to expand engagement mechanisms throughout the HTA life cycle. This dual-participation model demonstrated a scalable framework for global HTA practices, promoting inclusivity and transparency in healthcare decision-making.